I wish to study the mechanism of position-effect variegation in Drosophila melanogaster by a detailed study of its modification by: (1) alleles at the Su(var) locus and by (2) hyper- or hypoploidy for certain regions of centromeric heterochromatin. It is proposed that heterochromatic regions of DNA form a self-assembly complex with histones and heterochromatizing non-histone proteins. The suppressor Su(var) may code for a less effective protein in such an assembly in several heterochromatic regions. It is proposed to identify the heterochromatic components of rearrangements eliciting variegation susceptible to Su(var) modification, euchromatic regions thus susceptible, dose effects of hyper- or hypoploidy for the type allele at the locus, and diffusibility and temperature-sensitivity of the Su(var) effect. The possibility of regional differences in heterochromatic composition suggests that excess or deficiency for specific heterochromatin regions will suppress or enhance variegation due to rearrangement breaks in regions of similar composition; this possibility will also be tested.